Testing statistical hypothesis on random trees and applications to the protein classification problem
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Publication:2270660
Applications of Markov chains and discrete-time Markov processes on general state spaces (social mobility, learning theory, industrial processes, etc.) (60J20) Nonparametric hypothesis testing (62G10) Classification and discrimination; cluster analysis (statistical aspects) (62H30) Applications of statistics to biology and medical sciences; meta analysis (62P10) Applications of graph theory (05C90) Biochemistry, molecular biology (92C40) Random graphs (graph-theoretic aspects) (05C80)
Abstract: Efficient automatic protein classification is of central importance in genomic annotation. As an independent way to check the reliability of the classification, we propose a statistical approach to test if two sets of protein domain sequences coming from two families of the Pfam database are significantly different. We model protein sequences as realizations of Variable Length Markov Chains (VLMC) and we use the context trees as a signature of each protein family. Our approach is based on a Kolmogorov--Smirnov-type goodness-of-fit test proposed by Balding et al. [Limit theorems for sequences of random trees (2008), DOI: 10.1007/s11749-008-0092-z]. The test statistic is a supremum over the space of trees of a function of the two samples; its computation grows, in principle, exponentially fast with the maximal number of nodes of the potential trees. We show how to transform this problem into a max-flow over a related graph which can be solved using a Ford--Fulkerson algorithm in polynomial time on that number. We apply the test to 10 randomly chosen protein domain families from the seed of Pfam-A database (high quality, manually curated families). The test shows that the distributions of context trees coming from different families are significantly different. We emphasize that this is a novel mathematical approach to validate the automatic clustering of sequences in any context. We also study the performance of the test via simulations on Galton--Watson related processes.
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Cited in
(12)- Nonparametric statistical inference for the context tree of a stationary ergodic process
- A note on distinguishing random trees populations
- Variable length memory chains: characterization of stationary probability measures
- Limit theorems for sequences of random trees
- Overview of object oriented data analysis
- Entropy measures and the statistical analysis of protein family classification
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- Context tree selection: a unifying view
- Detecting renewal states in chains of variable length via intrinsic Bayes factors
- The statistical analysis of protein domain family distributions via Jaccard entropy measures
- A note on density estimation for binary sequences
- Perfect simulation of processes with long memory: a ``coupling into and from the past algorithm
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